Metastatic Voyage of Ovarian Cancer Cells in Ascites with the Assistance of Various Cellular Components

International Journal of Molecular Sciences

Mai Sugiyama¹  Akihiro Nawa¹  Yoshihiro Koya¹  Kazumasa Mogi²  Yoshihiko Yamakita²  Masato Yoshihara²  Kazuhisa Kitami²  Hiroaki Kajiyama²  Shohei Iyoshi²  Hiroki Fujimoto²  Kaname Uno²  Atsushi Enomoto³  Tomohiro Kanayama⁴  Hiroyuki Tomita⁴ 

[1] Bell Research Center, Department of Obstetrics and Gynecology Collaborative Research, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan;Department of Obstetrics and Gynecology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan;Department of Pathology, Graduate School of Medicine, Nagoya University, Nagoya 466-8560, Japan;Department of Tumor Pathology, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan;

关键词: ovarian cancer;    ascites;    spheroid;    hetero-cellular spheroid;    metastasis;    anoikis;   

DOI  :  10.3390/ijms23084383

来源: DOAJ

【 摘 要 】

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy and has a unique metastatic route using ascites, known as the transcoelomic root. However, studies on ascites and contained cellular components have not yet been sufficiently clarified. In this review, we focus on the significance of accumulating ascites, contained EOC cells in the form of spheroids, and interaction with non-malignant host cells. To become resistant against anoikis, EOC cells form spheroids in ascites, where epithelial-to-mesenchymal transition stimulated by transforming growth factor-β can be a key pathway. As spheroids form, EOC cells are also gaining the ability to attach and invade the peritoneum to induce intraperitoneal metastasis, as well as resistance to conventional chemotherapy. Recently, accumulating evidence suggests that EOC spheroids in ascites are composed of not only cancer cells, but also non-malignant cells existing with higher abundance than EOC cells in ascites, including macrophages, mesothelial cells, and lymphocytes. Moreover, hetero-cellular spheroids are demonstrated to form more aggregated spheroids and have higher adhesion ability for the mesothelial layer. To improve the poor prognosis, we need to elucidate the mechanisms of spheroid formation and interactions with non-malignant cells in ascites that are a unique tumor microenvironment for EOC.

【 授权许可】

Unknown